Enhanced eductor design

ABSTRACT

The present invention provides for an enhanced eductor element that significantly increases the amount of pressure generated at the siphon tube without significantly increasing the flow resistance through the eductor. The invention further provides for breath-actuated inhalation devices including the enhanced eductor element as an actuation mechanism.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/351,632, filed Nov. 15, 2016, which is a continuation of U.S. patentapplication Ser. No. 14/944,335, filed Nov. 18, 2015, now U.S. Pat. No.9,227,030, issued Jan. 5, 2016, which is a continuation of U.S. patentapplication Ser. No. 12/978,254, filed Dec. 23, 2010, now U.S. Pat. No.9,227,030, issued Apr. 4, 2017, which claims the benefit of U.S.Provisional Application No. 61/284,784, filed Dec. 23, 2009, each ofwhich is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

This present invention relates to metered dose inhaler devices andelements thereof for use in delivery of particulate medicaments by oralinhalation, and in particular to eductor elements having enhancedperformance and breath-actuated pressurized metered dose inhalers thatemploy such enhanced eductors to increase siphon pressure drop whileminimizing increased pressure drop over a range of operating flow rates.

BACKGROUND OF THE INVENTION

For many years, oral inhalation delivery of drug-laden aerosols to thelungs has been an effective means of drug delivery. One type of devicethat is effective for delivering particulate drugs is a metered doseinhaler, which includes a pressurized canister with a metering valvethat contains a drug formulation. In “press and breathe” versions ofmetered dose inhalers, the canister is placed within an actuatorcomprised of a housing that covers a lower portion of the canister,leaving the top portion exposed. The metering valve seats into asump/orifice assembly inside the base of the housing. The orifice ispositioned at an acute angle to the valve stem and directs discharge ofthe particulate drug formulation approximately through a conduitattached to the housing at a 90 degree angle and terminating in amouthpiece. To administer the drug, the user seals his/her lips aroundthe mouthpiece of the device and simultaneously inhales (an inspiratorybreath) while depressing the exposed portion of the canister into thehousing. The canister translates downward in a manner which actuates themetering valve and thus causes release of the drug as an aerosol plumewhich is then drawn into the respiratory tract as the user inhales. Itcan be difficult for some users to coordinate the release of the aerosolplume with their inspiratory breath.

In order to address problems with “press and breathe” actuated inhalers,improved inhaler devices have been developed that release the aerosolplume of drug automatically when the user takes in an inspiratorybreath. These are termed “breath-actuated pressurized meter doseinhalers” (“BApMDI”s). In exemplary BApMDI devices, actuation can becarried out using a spring that is compressed by opening a cover. Thisspring energy is stored until the BApMDI is triggered by the user'sbreath, at which time the spring force is applied to depress thepressurized canister and cause the release of a plume of aerosolizedmedication into the users' breath. Such triggering mechanisms dependupon an eductor element that includes a venturi having a flow path thatnarrows in a constriction zone and serves to increase the local velocityof the flow of inspiratory breath to create a siphon suitable to actuatethe device.

Although BApMDI devices represent an improvement in the art, it has beenfound that the energy (pressure drop) required to trigger the springenergy (and thus actuate the device) may exceed that which can beapplied by a normal human breath. This can particularly present aproblem where the user has compromised lung function, or where the useris an adolescent without the lung capacity of an adult. Thereaccordingly remains a need in the art to provide improved BApMDI deviceswith a triggering mechanism that enables actuation with a normal humanbreath.

SUMMARY OF THE INVENTION

It is an object of the invention to provide an enhanced eductor elementhaving improved performance characteristics. The invention arises fromthe discovery that introduction of a protrusion or structure into theconstriction zone surrounding the inlet apex of the siphon of aconventional eductor significantly increases the siphon pressure drop asa function of flow rate, without significantly increasing the pressuredrop across the eductor. This was unexpected and contrary to existingknowledge in the art that inclusion of any structure or modificationmember along the interior wall of the hollow bore of an eductor may helpincrease the siphon pressure drop of that element, however, it wouldalso result in higher pressure drop across the eductor and thus harm theperformance of the modified eductor. The enhanced eductor of the presentinvention can be used to reduce the inspiratory flow rate needed totrigger a breath-actuated inhaler device and therefore facilitate orallyinhaled medicament delivery for younger patients and for those patientswith compromised lung function.

In one aspect of the invention, an enhanced eductor element is providedthat includes: (a) a conduit with an inlet and an outlet; (b) an outersurface and an inner surface, where the inner surface forms a hollowbore that extends from the inlet to the outlet and is a generally smoothand continuous curvilinear surface; (c) a constriction zone that isformed by a reduction in the diameter of a portion of the hollow bore ata location that is between the inlet and the outlet, where theconstriction zone has a smaller diameter than the diameter of the maininlet and the outlet; (d) a modification member that is positioned uponthe inner surface hollow bore and in the constriction zone, wherein themodification member is a structure or protrusion that locally reducesthe diameter and cross-sectional area of the constriction zone; and (e)a siphon channel that establishes fluid communication between the outersurface of the eductor and the inner surface of the hollow bore throughsuch channel, where the channel is positioned adjacent to, or surroundedby the modification member.

In some variations, the enhanced eductor has a modification member witha height (H), and the constriction zone has a radius (R), where thephysical dimension of the modification member height (H) does not exceed0.65 times the physical dimension of the constriction zone radius (R).In other variations, the ratio of the physical dimension of themodification member height (H) to the physical dimension of theconstriction zone radius (R) is in the range of about 0.16 to about0.55. In still other variations, the enhanced eductor has a modificationmember with a length (L) along the main axis of the eductor, and theconstriction zone has a length (L_(CZ)) along the main axis of theeductor, where the physical dimension of the modification member length(L) does not exceed 0.75 times the physical dimension of theconstriction zone length (L_(CZ)). Additionally, the ratio of themodification member length (L) to the physical dimension of theconstriction zone length (L_(CZ)) may be between about 0.25 and about0.75. In other variations, the enhanced eductor has a modificationmember with a length (L) along the main axis of the eductor, and theconstriction zone has a radius (R), where the ratio of the physicaldimension of the modification member length (L) to the physicaldimension of the constriction zone radius (R) is in the range of about1.2 to about 3.0. Optionally, the modification member is sized such thatit decreases the cross-sectional area of the constriction zone by 21% orless; and/or the spread of the protrusion of the modification memberaround the perimeter of the constriction zone radius (R) may be between60 and 120 degrees. In still further variations, the presence of themodification member in the enhanced eductor element restricts the areafor airflow through the hollow bore by no more than 10% when compared toan eductor element without such a modification member, but having thesame inlet and outlet diameters, the same constriction zone diameter,and the same overall eductor length (L_(E)) as said enhanced eductor.

In another aspect of the invention, a breath-actuated inhalation deviceprovided. The device features an actuation assembly including anenhanced eductor element as described above, where air flowing throughthe eductor element with an inspired breath acts to create a lowpressure drop at the siphon channel that is suitable to actuate thedevice. In some variations, the breath-actuated inhalation device is apressurized meter dose inhaler. In other variations, the breath-actuatedinhalation device further includes a pressurized canister containing anaerosol formulation of drug particles, where the pressurized canisterfurther includes a primeless valve for release of the aerosolformulation into the device upon actuation of the device.

In a still further aspect of the invention, an eductor is provided. Theeductor includes an elongate conduit that has the following elements:(a) an outer surface and a bore forming an inner surface of the conduit,where the bore has a reduced diameter along a portion of the length ofthe elongate conduit to form a constriction zone; (b) an aperturelocated within the constriction zone, where the aperture forms a passagebetween the outer surface of the eductor and the bore; and (c) astructure that projects inwardly from the inner surface into the bore,where the structure is disposed adjacent to or around the aperture andthe presence of the structure generates an enhanced negative pressureadjacent to the aperture when a flow of fluid is moving through theelongate conduit, however the presence of the structure does notgenerate a substantial concomitant increase in pressure resistance tothe flow of fluid through the elongate conduit.

In some variations, the structure has a height (H), and the constrictionzone has a radius (R), where the physical dimension of the structureheight (H) does not exceed 0.65 times the physical dimension of theconstriction zone radius (R). In other variations, the ratio of thephysical dimension of the structure height (H) to the physical dimensionof the constriction zone radius (R) is in the range of about 0.16 toabout 0.55. In still other variations, the structure has a length (L)along the main axis of the conduit and the constriction zone has alength (L_(CZ)) along the main axis of the eductor, where the physicaldimension of the structure length (L) does not exceed 0.75 times thephysical dimension of the constriction zone length (L_(CZ)).Additionally, the ratio of the structure length (L) to the physicaldimension of the constriction zone length (L_(CZ)) can be between about0.25 and about 0.75. In other variations, the structure has a length (L)along the main axis of the conduit and the constriction zone has aradius (R), where the ratio of the physical dimension of the structurelength (L) to the physical dimension of the constriction zone radius (R)is in the range of about 1.2 to about 3.0. Optionally, the structure issized such that it decreases the cross-sectional area of theconstriction zone by 21% or less. In still further variations, thepresence of the structure in the eductor restricts airflow through thebore by no more than 10% when compared to an eductor without such astructure, but otherwise having the same physical dimensions as theeductor.

In another aspect of the invention, a breath-actuated inhalation deviceprovided. The device features an actuation assembly including theeductor as described above, where air flowing through the eductor withan inspired breath acts to create a low pressure drop at the siphonchannel that is suitable to actuate the device. In some variations, thebreath-actuated inhalation device is a pressurized meter dose inhaler.In other variations, the breath-actuated inhalation device furtherincludes a pressurized canister containing an aerosol formulation ofdrug particles, where the pressurized canister further includes aprimeless valve for release of the aerosol formulation into the deviceupon actuation of the device.

It is a particular advantage of the present invention that improvedperformance can be obtained from eductor elements that have beenmodified in accordance with the invention. The enhanced eductors can beused in a breath-actuated pressurized meter dose inhaler (BApMDI) deviceto increase the local velocity of the flow of inspiratory breath andcreate a siphon suitable to actuate the device, enabling patients withcompromised lung function, or adolescents without significant lungfunction to use these convenient and efficient drug delivery devices. Itis also a particular advantage of the present invention that simple andreproducible methods of production can be used to produce the enhancedeductors of the invention.

These and other objects, aspects, variations and advantages of thepresent invention will readily occur to the person of ordinary skill inthe art upon reading the instant disclosure and specification.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional representation of a conventional eductorelement.

FIG. 2 is a perspective cutaway view of the conventional eductor elementof FIG. 1.

FIG. 3 is a schematic depiction of a conventional eductor elementshowing various important parameters thereof.

FIG. 4 is a cross-sectional representation of an enhanced eductorelement produced in accordance with the invention.

FIG. 5 is a perspective cutaway view of the enhanced eductor element ofFIG. 4.

FIG. 6A is a cutaway side perspective view of the modification member ofthe enhanced eductor embodiment of FIGS. 4 and 5, wherein the length (L)of the modification member along the long axis of the construction zoneis shown relative to the overall length of the construction zone (Lg) inFIG. 6C.

FIG. 6B is a cutaway axial view of the modification member of theenhanced eductor embodiment of FIGS. 4 and 5.

FIG. 6C is a side perspective view of the constriction zone of theenhanced eductor embodiment of FIGS. 4 and 5.

FIG. 7 depicts the performance test results (siphon pressure dropplotted against concomitant pressure drop across the eductor) for twoeductor elements, a conventional eductor and an enhanced eductor elementproduced in accordance with the invention.

FIG. 8A presents the performance test results (a plot of themodification member height (H) against the siphon pressure drop at twodifferent fluid flow rates) for enhanced eductors elements having Light,Medium and Heavy modification members produced in accordance with theinvention.

FIG. 8B presents the performance test results (a plot of themodification member height (H) against the eductor resistance (pressuredrop across the eductor) at two different fluid flow rates for enhancedeductors elements having Light, Medium and Heavy modification membersproduced in accordance with the invention.

FIG. 9A compares the performance test results (a plot of themodification member height (H) against the siphon pressure drop at twodifferent fluid flow rates) for a conventional eductor and an enhancedeductor produced in accordance with the invention.

FIG. 9B compares the performance test results (a plot of themodification member height (H) against the eductor resistance (pressuredrop across the eductor) at two different fluid flow rates) for aconventional eductor and an enhanced eductor produced in accordance withthe invention.

FIG. 10 depicts a cutaway view of a BApMDI device incorporating anenhanced eductor produced according to the present invention as theactuation mechanism.

DETAILED DESCRIPTION OF THE INVENTION

Before describing the present invention in detail, it is to beunderstood that the present invention is not limited to particularlyexemplified eductor elements, breath actuated pressurized metered doseinhaler devices, or manufacturing process parameters as such may, ofcourse, vary. It is also to be understood that the technical terminologyused herein is for the purpose of describing particular embodiments ofthe invention only, and is not intended to be limiting.

All publications, patents and patent applications cited herein, whethersupra or infra, are hereby incorporated by reference in their entirety.

As used herein, an “eductor” is an elongate conduit (hollow bore orchannel) or venturi having an inlet and an outlet and through whichfluid is drawn or pumped under the influence of a pressure drop appliedacross the inlet and outlet of the eductor. The hollow bore through theconduit usually has a cylindrical cross section, but can haveellipsoidal, oval, smoothed rectangular or other nonsymmetricalcross-section. The hollow bore has a constriction zone located withinit, wherein the inlet diameter converges to a smaller diameter for aportion of the axial length to form a constriction zone, which thendiverges to a diameter at the outlet that is close to that of the inlet.The convergent half angle is usually in the range of 17 to 25 degreesoff the axial centerline. The divergent half angle is usually 3.5 to 7.5degrees off the axial centerline. The axial length of the constrictionzone is usually in the range of 2 to 5 diameters of the hollow bore. Theratio of the inlet diameter to the constriction diameter is referred toas choke or 1/β. As fluid passes though the eductor within theconstriction zone, a reduced pressure is produced as a result inincreased velocity of the fluid flow through the constriction zone, theresult of a Venturi Effect as described by Bernoulli's Equation. Asiphon tube penetrates the conduit from the outside wall (siphon inlet)of the eductor to a location on the inside wall (siphon outlet) of thetubular duct that coincides axially with the constriction zone. Due tothe Venturi Effect, named after Giovanni Venturi, a pressure drop isgenerated across the siphon channel that is equal to the difference inthe pressure at the outside wall of the eductor, less the pressure atthe inside wall of the tubular duct. The siphon pressure drop can beused to draw fluid through the siphon tube and into the tube.

Eductors are useful in many commercial applications. Eductors can beused as tank mixers. By submersing an eductor into the contents of atank and pumping fluid through the eductor, the eductor will draw in upto 4-5 volumes of fluid for each volume pumped through the eductor. Inthis manner, with the use of an eductor, the same amount of mixing canbe achieved with the use of a much smaller pump.

Eductors are also useful in the generation of foam for fire fightingapplications. In such applications, water is pumped through an eductorthat is a component for a special foaming nozzle. The water flow throughthe eductor draws in various foaming agents. Air is then pumped ontothis mixture such that a foam is ejected from the nozzle and used toextinguish certain types of fire. Eductors are also very useful when aflammable liquid needs to be pumped and it would be dangerous to pumpthe flammable liquid directly with a pump.

A cross-sectional view of a conventional eductor is depicted in FIG. 1.In the figure, Arrow A shows the direction of fluid flow through HollowBore (110) of the Eductor (100), going from the Eductor Inlet (115) tothe Eductor Outlet (120). The Siphon Inlet (115) narrows to aConstriction Zone (125). The Siphon Inlet (140) is located within theEductor Wall (135) at a point within the Constriction Zone (125). Thereis a Siphon Channel (130) which penetrates the Side Wall (135) of theEductor and penetrates through the Inner Wall (150) at Siphon Outlet(160). The surface of the Inner Wall (150) is smooth and continuous atSiphon Outlet (160) and all along the whole length of the Hollow Bore(110). This is because standard teaching provides that there should beno irregularities on the inner surface of an eductor which would causeturbulence in the fluid flow and thereby reduce the efficiency of theeductor. FIG. 2 depicts a perspective cutaway view of the Eductor (100)of FIG. 1, where Arrow A shows the direction of fluid flow through theHollow Bore (110). Accelerated fluid flow over Siphon Outlet (160)causes a pressure drop to be drawn on the Siphon Inlet (140).

Conventional eductors such as those depicted in FIGS. 1 and 2 can beused in BApMDI devices to increase the local velocity of the flow ofinspiratory breath to create a siphon suitable to actuate the device.Exemplary BApMDI devices include those devices described in U.S. Pat.Nos. 5,954,047; 6,026,808; and 6,905,141 where spring energy can betriggered by a user's breath to actuate the device. In addition,eductors are incorporated in the inhaler devices described in U.S. Pat.Nos. 5,657,749 and 6,948,496. In operation, the eductors generallyconsist of a venturi with a flow path diameter that narrows from theinlet to a constricted zone which increases the local velocity of theinspiratory flow. The siphon is located within the constricted zone and,per Bernoulli's Equation, the increased velocity over the Inlet Apex ofthe siphon generates a pressure (P_(Inlet Apex)) that is lower than theAmbient pressure (P_(Ambient)) entering the eductor, thus creating asiphon. In BApMDI devices, the siphon is connected to a variable volumechamber. As the siphon draws air into the constricted region of theeductor the variable volume chamber is evacuated. At a triggering point,the variable volume chamber has been evacuated sufficiently to collapse,thus tripping the discharging mechanism of the BApMDI (e.g., release ofa compressed spring). By appropriate selection of design parameters,such as the chamber volume, the eductor size, shape and configuration,and the siphon diameter, the BApMDI device can be designed to causeactuation with a desired amount of force of the inspiratory breath. Thismechanism enables consistent discharge timing that is appropriate forlung delivery and automatically adjusts to the inspiratory pattern for awide range of users.

It is generally understood in the art that, by applying Bernoulli'sequation, the siphon pressure drop generated by an eductor can beincreased by narrowing the diameter of the constricted zone, that is, byincreasing the choke of the eductor. This can be a very useful parameterto adjust the triggering mechanism in BApMDI devices for configurationswhere considerable force is required to actuate the device in a timelymanner. However, as the constriction zone diameter narrows, it becomesharder to move air through the eductor and the pressure drop across theeductor increases according to Pousieulles' Equation. As a result,modification of an eductor to increase constriction (choke) might rendera BApMDI device inoperative as some users may not have sufficientpulmonary function to trigger a device with such increased constrictionand increased eductor pressure drop. Accordingly, there is a significantengineering trade-off in terms of designing an improved eductor for usein a BApMDI device. Specifically, any increases in the constriction(increased choke) of the eductor would be expected to cause aconcomitant increase in the pressure drop drawn on the siphon tube (thesiphon pressure drop), and thereby increase actuation force. However,any such decrease in the diameter of the constriction zone would cause agreater resistance to fluid flow through the eductor, resulting in apressure drop across the eductor, possibly frustrating any increasesrealized with the enhanced siphon pressure drop. This can be thought ofas trying to draw fluid from a cup through a series of smaller andsmaller straws. Accordingly, application of the engineering technique ofsignificantly increasing choke to increase the siphon pressure drop (andthus increase actuation force) would be expected to render the eductorinoperative, since a user trying to inspire through the constrictedeductor would find it difficult or impossible to draw a normal breathacross such an eductor having such a significant constriction.

It has been serendipitously discovered that introducing a protrusion orstructure (effectively, a structural constriction) occupying a highlylocalized area within the constriction zone adjacent to the apex of thesiphon inlet can dramatically increase the siphon pressure drop in aneductor without significantly increasing the pressure drop across theeductor. These localized structures or protrusions are referred toherein as a “modification member”. Use of the enhanced eductor design ina BApMDI device to actuate the device means that even compromised userscan now actuate such devices even if they require an increased siphonpressure drop to operate the device correctly. The modification member(highly localized protrusion or structure) was unintentionallydiscovered when the inventors inserted a sharp probe into the siphonaperture of a conventional eductor from outside of the eductor as partof the process of inserting that eductor into a bench testing apparatus.Insertion of the probe into the plastic eductor aperture causeddeformation of the plastic around the inside perimeter of the apertureand the creation of a small conical frustum-shaped protrusion in theconstriction zone bore of the eductor. Upon subsequent testing of theeductor performance with the bench testing apparatus, the eductor siphonpressure was found to dramatically increase, however there was nosignificant (deleterious) pressure drop across the eductor. Subsequenttesting confirmed the phenomena, and specific modifications have nowbeen designed into the enhanced eductor designs (and injection moldingequipment fabricated) to create effective modification members in theconstriction zone of the eductor.

Referring now to FIG. 3, in order to describe the present invention,several important features of an eductor are depicted. Three primaryparameters of the eductor include the length of the eductor (L_(E)), theinside diameter of the inlet (D_(i)) and the inside diameter of theoutlet (D_(o)). Another important parameter is the diameter of thethroat (D_(t)). The eductor narrows from D_(i) to D_(t) through what iscalled the convergent zone. There is then a region having the diameterof the throat (D_(t)) which is called the constriction zone. Then thediameter increases again until outlet diameter (D_(o)) is reached whichis usually equal to the inlet diameter (D_(i)). This region is calledthe divergent region. Siphon pressure drop, and pressure drop across theeductor can be determined using the following measurements: the pressureat the inlet (P_(Inlet)) of the eductor; the pressure at the outlet(P_(Outlet)) of the eductor; the ambient pressure entering the eductorat the siphon (P_(Ambient)); and the pressure at the apex of the inlet(P_(Inlet Apex)).

With reference to “Fluid Meters, Their Theory and Application, Report ofASME Research Committee on FluidMeters”, 6^(th) Edition (1971), thesiphon pressure drop (ΔP_(siphon)) generated by the eductor siphon isdescribed by Bernolli's Equation for invisid subMach 1 flow:

ΔP _(siphon)=(P _(Ambient) −P _(Inlet Apex))=Q ²ρ(1/A ²−1/a ²)2g_(c)(g_(f)/cm²), where:

ρ=standard temperature and pressure (STP) air densitythroughout=0.001193 gm/cm³;

g_(c)=gravitational constant=982.14 (g_(m)/g_(f))(cm/sec²);

a=throat cross sectional area=7πD_(t) ²/4; and

A=Inlet cross sectional area=7πD_(i) ²/4.

The flow and pressure drop through any conduit with laminar flow can bedescribed by Poiseulle's Equation:

Q=volumetric flowrate=g_(c)ρ(P _(Inlet) −P _(Outlet))d ⁴/128mL_(E)(cm³/sec).

Thus, the pressure drop across the eductor (ΔP_(eductor)) can then bedetermined by rearranging Pouiseulle's Equation and including a lossfactor (1−ΔP_(Eloss)) which is a function of the venturi α₂ and β:

ΔP _(eductor)=(P _(Inlet) −P _(Outlet))=Q128 μL_(E)/πg_(c) D _(mean)⁴(1−ΔP _(Eloss))(g_(f)/cm²), where:

α₂=divergent nozzle ½ angle=7.5 degrees;

β=throat diameter divided by the inlet diameter (D_(t)/D_(i))=0.339g_(m)/sec-cm; air viscosity at STP μ_(air)=0.000179; and

ΔP_(Eloss)=diff. Pressure Loss(%)=e^((1.883+(0.253α2)+(−0.327βα2)+(0.494β)))

Using the above-described mathematical techniques, both the siphonpressure drop and the pressure drop across the entire eductor can bepredicted at various flow rates for proposed eductor designs of knowndimensions. These predicted pressure drops can then be compared tomeasured pressure drop values of various model eductors. Surprisingly,when the above-described techniques are applied to the enhanced eductordesigns of the present invention, the predicted values fail toadequately describe the measured eductor performance. In particular,when there is a predicted increase in siphon pressure drop (based uponthe added constriction provided by the modification member in theconstriction zone), the corresponding predicted values for pressure dropacross the eductor significantly over-estimate the magnitude of thatpressure drop. In fact, significant increases in siphon pressure dropcan be achieved with the enhanced eductor designs of the presentinvention without a concomitant unwanted increase in pressure dropacross the eductor. In some cases, the enhanced eductor designs of thepresent invention significantly increase siphon pressure drop with aminimal reduction in pressure drop across the eductor of 10% or less.This results in eductor designs that have dramatically improvedperformance characteristics.

The enhanced eductors of the present invention comprise a modificationmember (protrusion or structure) that is located on the inner wall ofthe eductor in the constriction zone. The size and shape of theprotrusion or protrusion is restricted to a volume surrounding thesiphon outlet, defined by a length (L) along the long axis of theconstriction zone, a height (H) which is the maximum amount that theprotrusion or structure projects above the surface of the constrictionzone, and a segment of the curvilinear surface (θ or Theta) formed bythe constriction zone wall (a cross-sectional arc having an anglerelative to the minor axis of the constriction zone). In certainembodiments, the siphon channel extends through the modification member,and preferably the siphon channel extends through the axial middle ofthe protrusion or structure that forms the modification member. In otherembodiments, the protrusion or structure is adjacent to the siphonoutlet. The protrusion or structure causes an increased reduction inpressure just in the location surrounding the siphon inlet apex, whichincreases the local velocity of the fluid flow and results in areduction of pressure at the apex. There is however little or noincrease in flow resistance because of the decrease in thecross-sectional area of the eductor conduit if the following keyparameters of the protrusion or structure are met: the height (H) of theprotrusion or structure does not exceed 0.65 times the radius (R) of theconstriction zone; the length of the protrusion or structure along theeductor long axis (L) does not exceed 0.75 times the length of theconstriction zone (L_(CZ)); and the spread of the protrusion orstructure around the perimeter of the constriction zone radius (θ) doesnot exceed 120 degrees, such that the protrusion or structure that formsthe modification member decreases the constriction zone cross-sectionalarea by about 21% or less. In certain embodiments, the ratio between theheight (H) of the protrusion or structure and the radius (R) of theconstriction zone is between about 0.16 and 0.55. In furtherembodiments, the ratio between the length of the protrusion or structurealong the eductor long axis (L) and the radius (R) of the constrictionzone is between about 1.2 and 3.0. In still further embodiments, thespread of the protrusion or structure around the perimeter of theconstriction zone radius (θ) is between about 30 and 80 degrees.

A cross-sectional view of an embodiment of an enhanced eductor of thepresent invention is depicted in FIG. 4. In the figure, Arrow A showsthe direction of fluid flow through Hollow Bore (210) of the Eductor(200) going from the Eductor Inlet (215) to the Eductor Outlet (220).The Siphon Inlet (215) narrows to a Constriction Zone (225). The SiphonInlet (240) is located within the Eductor Wall (235) at a point withinthe Constriction Zone (225). There is a Siphon Channel (230) whichpenetrates Side Wall (235), and passes through the Inner Wall (250). TheSiphon Channel (230) also passes through the protrusion or structureprovided by the Modification Member (265), and terminates at the SiphonOutlet (260). FIG. 5 depicts a perspective cutaway view of the Eductor(200) of FIG. 4, where Arrow A shows the direction of fluid flow throughthe Hollow Bore (210). Accelerated fluid flow over the ModificationMember (265) and Siphon Outlet (260) causes an enhanced siphon pressuredrop to be drawn on the Siphon Inlet (240) without a concomitantinappropriate increase in the pressure drop across the eductor.Accordingly, there is little to no significant increase in flowresistance through the eductor despite the decrease in thecross-sectional area of the constriction zone in the eductor bore.

FIG. 6A is a cutaway side perspective view of the Modification Member(265) of eductor embodiment of FIGS. 4 and 5, wherein the length (L) ofthe Modification Member along the long axis of the constriction zone isshown relative to the overall length of the constriction zone (L_(CZ))in the embodiment of FIGS. 4 and 5. FIG. 6B is a cutaway axial view ofthe Modification Member (265) of the eductor embodiment of FIGS. 4 and5, wherein the height (H) of the Modification Member (265), and thesegment of the curvilinear surface (θ) formed by the constriction zonewall of the modification member is also shown.

In order to demonstrate the improved performance of an enhanced eductorelement according to the present invention, two eductors havingidentical primary eductor parameters (identical eductor lengths (L_(E)),identical inlet inside diameters (D_(i)), identical outlet insidediameters (D_(o)), identical throat diameters (D_(t)), and identicalconstriction zone lengths (L_(CZ))) were produced. The first eductor(002) was a conventional eductor, and the second eductor (003) includeda modification member in the constriction zone produced in accordancewith the present invention. The two eductor elements were tested forsiphon pressure drop and for pressure drop across the eductor. FIG. 7depicts the results of the testing of the eductors at various flowrates, in particular, showing a plot of the flow through the eductorhorizontal axes as plotted against the siphon pressure drop (verticalaxis) generated for the conventional eductor (002) and the enhancedeductor (003) that was modified according to the present invention.There are 4 data points located at each horizontal data point. Thediamond (♦) represents the resistance (pressure drop across the eductor)through the conventional eductor (002), and the triangle (▴) representsthe resistance (pressure drop across the eductor) through the enhancedeductor (003). As can be seen, at the various test flow rates (5, 10,15, 20, 25, 30, 35, 40, 45, and 55 liters per minute (LPM)), the twodata points (♦ and ▴) representing the pressure drop across the eductorsfor the two different educators are almost identical, demonstrating thatthe addition of the modification member in the enhanced eductor (003)did not result in the increase in flow resistance through that eductordespite the decrease in the cross-sectional area of the constrictionzone in the eductor bore.

However, when the siphon pressure drop for the two eductors wasmeasured, there was a significant difference seen between the conventioneductor (002) and the enhanced eductor (003). Referring again to FIG. 7,the siphon pressure drop generated at the siphon outlet for theconventional eductor (002) is represented by the circle (●), and thesiphon pressure drop generated at the siphon outlet for the enhancedeductor (003) is represented by the square (▪). As can be seen, as theflow rate value increases (going from left to right along the horizontalaxis) the difference between the siphon pressure drop for the conventioneductor (002) and the enhanced educator (003) increases significantly.For example, at 40 LPM (generally the velocity of a normal inspiratorybreath), the enhanced eductor siphon pressure drop (▪) is almost 60 mbarhigher than that for the conventional eductor pressure drop (●), whichis surprising since the concomitant pressure drop across both eductorsvaried from one another by only about 2-3 mbar. In fact, at most of theflow rates associated with a normal inspiratory breath (25 to 40 LPM),the enhanced eductor (003) had significantly increased siphon pressuredrop and a concomitant lower resistance (pressure drop across theeductor) when compared to the conventional eductor (002). This was anunexpected result in light of typical eductor design principals whichteach that any increase in the obstruction of a flow path (presence ofthe modification member) should result in a higher resistance.

In order to further demonstrate the improved performance of enhancedeductor elements produced according to the present invention, a numberof eductors having identical primary eductor parameters (identicaleductor lengths (L_(E)), identical inlet inside diameters (D_(i)),identical outlet inside diameters (D_(o)), identical throat diameters(D_(t)), and identical constriction zone lengths (L_(CZ))) wereproduced. The first eductor (Rev 002) was a conventional eductorproduced by injection molding. The second eductor (Rev 003) was alsoproduced by injection molding and included a molded modification member(with a protrusion height (H) of 0.45 mm) in the constriction zone andencircling the siphon outlet to form an enhanced eductor element inaccordance with the present invention. Next, conventional eductorsproduced by the same injection molding process used to produce the (Rev002) eductor were hand-altered to produce three groups of modificationmembers in accordance with the present invention. In particular, threegroups of enhanced eductors, referred to herein as Heavy, Medium andLight, respectively, were formed manually by the introduction of atapered tool into the siphon channel. Insertion of the tapered tool intothe siphon channel caused deformation of the molded plastic of theeductor, resulting in “volcano-shaped” modification members within thehollow bore of the eductor and encircling the siphon outlet. The amountof force used to insert the tapered tool was subjectively applied asLight, Medium and Heavy to produce modification members having a rangeof different protrusion heights (H). The actual protrusion height (H)for each eductor element in the Light, Medium and Heavy modificationmember groups was then measured optically. The diameter of the hollowbore in the constriction zone of all of the eductor elements was 2.54mm, and thus the radius (R) of the constriction zone was 1.27 mm. Theoptically measured heights (H) of the modification members in the Light,Medium and Heavy enhanced eductor groups ranged from about 0.2 mm toabout 0.7 mm.

Referring now to FIG. 8A, a plot of the modification member heights (H)vs the siphon pressure drop at two flow rates (28.3 LPM and 45 LPM) forthe Light, Medium and Heavy modification member groups is presented. Ascan be seen, all of the hand-modified enhanced eductors showed increasedeductor efficiency, where the siphon pressure drop at the lower fluidflow rate (28.3 LPM) ranged from about 80 mbar (for the Lightmodification member group) to about 120 mbar (for the Heavy modificationmember group). The siphon pressure drop at the higher fluid flow rate(45 LPM) ranged from about 250 mbar (for the Light modification membergroup) to about 375 mbar (for the Heavy modification member group). Theconcomitant eductor resistance (pressure drop across the eductor) forthe Light, Medium and Heavy modification member groups is presented inFIG. 8B. In particular, a plot of the modification member heights (H)against the eductor resistance (pressure drop across the eductor) at twoflow rates (28.3 LPM and 45 LPM) for the Light, Medium and Heavymodification member groups is presented in FIG. 8B. As can be seen, theeductor resistance at the lower flow rate (28.3 LPM) ranges from about0.060 KPa{circumflex over ( )}0.5/LPM (for the Light modification membergroup) to about 0.063 KPa{circumflex over ( )}0.5/LPM (for the Heavymodification member group). The eductor resistance at the higher fluidflow rate (45 LPM) ranged from about 0.063 KPa{circumflex over( )}0.5/LPM (for the Light modification member group) to about 0.070KPa{circumflex over ( )}0.5/LPM (for the Heavy modification membergroup). Accordingly, even though the Light, Medium and Heavymodification member groups showed significantly enhanced siphon pressuredrop performance that increased in a substantially linear fashion withincreases in the height (H) of the modification members, the concomitanteductor resistance performance remained relatively unchanged across allthree groups.

In comparison to the eductor performance results obtained with thehand-modified enhanced eductors (the Light, Medium and Heavymodification member groups), the performance of the conventional eductor(Rev 002) and the injection molded enhanced eductor (Rev 003) weretested using the same test parameters. Referring now to FIG. 9A, a plotof the modification member heights (H) against the siphon pressure dropat two flow rates (28.3 LPM and 45 LPM) for the conventional eductor(Rev 002), where (H)=0, and the injection molded enhanced eductor (Rev003), where (H)=0.45 mm, is presented. As can be seen, the enhancedeductor (Rev 003) showed increased eductor efficiency as compared withthe conventional eductor (Rev 002), where the siphon pressure drop atthe lower fluid flow rate (28.3 LPM) was about 60 mbar (for the Rev 002conventional eductor) as compared with about 250 mbar (for the Rev 003enhanced eductor); and the siphon pressure drop at the higher fluid flowrate (45 LPM) was about 175 mbar (for the Rev 002 conventional eductor)as compared to about 255 mbar (for the Rev 003 enhanced eductor). Theconcomitant eductor resistance results (pressure drop across theeductor) for the conventional eductor (Rev 002) and the injection moldedenhanced eductor (Rev 003) are presented in FIG. 9B. In particular, aplot of the modification member heights (H) against the eductorresistance (pressure drop across the eductor) at two flow rates (28.3LPM and 45 LPM) for the conventional eductor (Rev 002) and theinjection-molded enhanced eductor (Rev 003) is presented in FIG. 9B. Ascan be seen, the eductor resistance at the lower flow rate (28.3 LPM)was about 0.059-0.060 KPa{circumflex over ( )}0.5/LPM for the Rev 002conventional eductor (as compared to about 0.053-0.055 KPa{circumflexover ( )}0.5/LPM for the Rev 003 enhanced eductor). The eductorresistance at the higher fluid flow rate (45 LPM) was about 0.059KPa{circumflex over ( )}0.5/LPM for the Rev 002 conventional eductor (ascompared to about 0.057 KPa{circumflex over ( )}0.5/LPM for the Rev 003enhanced eductor). Accordingly, the enhanced eductor (Rev 003)demonstrated comparable performance enhancements with the Light, Mediumand Heavy modification member enhanced eductors (increased siphon dropwithout a concomitant increase in resistance pressure), and wasdemonstrably superior to the convention eductor (Rev 002) in both siphonpressure drop and resistance pressure performance.

Yet a further example of the benefits provided by the enhanced eductordesigns of the present invention is that the enhanced eductors display agreatly improved triggering consistency, a key quality performanceattribute for BApMDIs. In this regard, BApMDI devices containing eductorelements must be quality tested to demonstrate acceptability for use ina human pharmaceutical product. Accordingly, devices that have beenmanufactured for use in human pharmaceutical products are tested foractuation pressure performance and consistency to ensure acceptablepharmaceutical performance. The testing parameters set an acceptableupper and lower limit of device (breath) actuation pressure at 47 and 25mbar, respectively. The lower limit is set at a high enough pressure toavoid accidental triggering of the inhaler, and the upper limit is setat an empirically set value which reflects an upper value forinspiratory breath pressure which a normal person would findcomfortable. In quality testing of the required actuation pressure for asampling of BApMDI devices containing a conventional eductor, asignificant number of units tested were found to be well above the upperactuation pressure limit, and 70% of the tested devices therefore failedto meet the quality specification. However, when a similar sampling ofBApMDI devices containing an enhanced eductor element produced inaccordance with the present invention were quality tested, only 15% ofthe tested devices failed to meet the quality specification. Thisrepresents a significant improvement in manufacturing efficiency as aresult of switching from the use of a conventional eductor to theeductors of the present invention, which can be reflected in significantimprovement in the overall cost of goods for such pharmaceuticalproducts.

The enhanced eductors of the present invention may be manufactured usingstandard processes and techniques known to the person of ordinary skillin the art and using materials that are readily available. Accordingly,enhanced eductors can be formed from plastic materials, e.g.,pharmaceutical grade plastics such as polycarbonates (Makrolon, partnumber 2458-550115, Bayer MaterialScience), using a standard injectionmolding process. In one preferred embodiment, the enhanced eductors areformed from a polycarbonate material using an injection moldingtechnique employing three pins (one pin extending from the eductor inletto the middle of the modification member over the middle of the siphonoutlet; a second pin extending from the eductor outlet to the middle ofthe modification member over the middle of the siphon outlet and meetingthe first pin; and a third pin extending from the siphon inlet to thesiphon outlet and meeting the first and second pins). The moldcomponents including the pins are preferably finely polished to avoidgeneration of any surface irregularities on the inside surface and alongthe entire length of the eductor bore including the surfaces of themodification member.

Once manufactured, there are numerous applications where the enhancedeductors of the present invention may be advantageously applied. Onesuch application is in the triggering mechanism of a breath-actuatedinhaler, where a human inhalation provides the triggering energy foractuation of the device. In this regard, it is often the case that theenergy (pressure drop) required to trigger a breath-actuated inhaler isgreater than that which can be applied by a normal human breath. Thisinstant invention provides a means to amplify the pressure drop acrossthe siphon, which if advantageously coupled to a triggering mechanismenables actuation with a normal human breath. The ability to increasethe pressure drop across the siphon of the enhanced eductor without aproportionate increase in the eductor pressure drop enables even humansubjects such as small children and those compromised by healthconditions to operate a breath-actuated triggering mechanism.

Delivery of drugs, either local or systemically, via delivery ofpowders, mists and aerosols to the lungs has been in use for decades.Nebulizers typically generate mists or aerosols which are delivered intothe air stream being inhaled by the patient. The aerosols and mists areoften generated by forcing compressed air through a solution of themedication or by the use of vibrating meshes which force the solution ofthe medication through apertures in the mesh to generate very smalldroplets of the medication solution. The generated aerosol is deliveredto the patient by way of tubing and/or a face mask which is held inplace over the nose and mouth of the patient who breathes in normally.The advantage of this feature is that the patient is only required tobreathe in through the face mask in a normal fashion. There is no needto synchronize the breathing with the nebulizer, because the nebulizercontinuously delivers the medicated mist to the patient which makes anebulizer particularly useful for treating pediatric patients.

For non-pediatric patients, metered dose inhalers (MDIs, also referredto as pressurized MDIs or pMDIs) were developed, which are hand-held anddo not require ancillary equipment or electricity. MDI devices typicallyconsist of a small aluminum canister containing pressurized gas and amedication formulation, which is either a solution and/or a suspensionof the medication. The canisters have a metering valve which willdeliver a single small bolus (typically 25-100 mL) of the formulationwhen the stem of the valve is compressed. The MDI inhaler device can bemade up of a simple plastic housing into which the canister is insertedwith the valve end of the canister placed into the housing. A portion ofthe bottom of the canister is exposed above the housing so that it canbe manually pushed further down into the housing. This action causes thevalve stem to be pushed into the body of the valve and releases a bolusof the medication into the housing.

In use, a patient holds the mouthpiece of the MDI device up to his/hermouth, starts to take a breath and then manually releases a bolus of themedication by pushing down on the canister. This releases an aerosolbolus of the medication into the air stream created by the inhalation ofthe patient. This combination of manual dexterity and breath timingeffectively excludes small children from using MDI devices effectively,but a number of adults also find it difficult to use such MDI devicesproperly. In order to address these concerns, breath-actuated MDIdevices were developed. Early versions included advanced housings intowhich a standard manual MDI device is placed. There are both mechanicaland electronic versions which detect the air flow caused by the patientinhaling and then cause the canister to be automatically depressed inorder to deliver the medication.

There are a number of breath-actuated inhaler devices in which thepressurized canister is activated in various ways by the flow ofinspiratory breath of the patient. Many are activated by placing apivotable plate that is positioned in the air flow and mechanicallylinked so that rotation of the plate triggers the release of some typeof stored energy to activate a metered dose inhaler (MDI) canistervalve. U.S. Pat. Nos. 5,954,047; 6,026,808; and 6,905,141 describe abreath-actuated pressurized MDI (BApMDI) device in which a spring iscompressed by opening a cover and then the stored energy of the springis released by the patient breathing in though the mouthpiece. The flowof inspiratory air moves through a conventional eductor which causes thevolume of a variable volume chamber to be reduced by the vacuum drawn onthe vacuum chamber through the siphon tube. As the vacuum chamber sizedecreases, this mechanically causes a trigger to be released and thestored spring energy to bias the medicament canister downwards whichactivates the metering valve and dispenses a dose of the medicament.There are various such BApMDI devices currently being manufactured, suchas the TEMPO® BApMDI device (MAP Pharmaceuticals), and the Maxair®Autohaler®, and EasiBreathe MDI devices (Teva). Because the enhancedeductors of the present invention can, in effect, be used to amplify theforce of any fluid flow, such elements can be used in any type of deviceor apparatus where such pressure amplification would be of benefit.

In certain embodiments of the invention, the enhanced eductor is used toprovide an improved version of a TEMPO BApMDI device (MAPPharmaceuticals, Inc.). This device includes the breath-actuated MDIinhaler device (actuator) containing a pressurized canister, having aprimeless valve assembly and containing an aerosol formulation with asuspension of powdered medicament. The valve assembly contains athermoplastic core, body, and metering chamber and a spring. The valveassembly has been specifically designed to allow the pressurizedcontents of the canister to freely flow into and out of the meteringchamber. The free flow of the formulation into and out of the meteringchamber is achieved by the specific design of the flow path between thecanister and the metering chamber. As the valve primes when it isinverted for use, there is no need to fire any wasted priming shots. Thevalve is intended to be used in the inverted (valve down) orientation,with a suitable delivery actuator.

The valve is actuated by depressing the core into the valve (by pushingonto the canister base on inverted valve when used with an actuator).The valve is designed such that on depressing the core and prior to theside hole of the core entering the metering chamber, the slot at thelower end of the core within the chamber passes beyond the inner seat,closing the chamber to the formulation. Further depression of the coreallows the side hole of the core to enter the metering chamber,permitting it to discharge the formulation through the hollow stem. Whenthe core is returned by the spring to its rest position, the slot at thelower end of the core enters the metering chamber allowing the chamberto be refilled. The valve is thus primeless and specifically intended todischarge metered doses of formulation.

The TEMPO inhaler is an actuator that allows for breath-synchronizeddrug formulation delivery from the filled canister to the patient'slungs. It automatically dispenses drug when the patient inhales andenables drug delivery to the deep lung. The inhaler discharges themetered dose of aerosol into a small integral flow control chamber(FCC). The aerosol plume is slowed in this chamber by spinning the plumeinto a vortex to increase residence time, and by buffeting the plumewith perpendicular sidewall airflows to reduce sidewall deposition. Theincreased residence time allows for evaporation of the formulationpropellant, leaving a high proportion of respirable drug particles inthe emitted plume. The breath-synchronized trigger of the inhaler isdesigned to actuate the filled canister and discharge the plume withinthe first half of the inspiratory cycle (exchange volume), independentof peak flow rate or inspiratory volume.

The trigger and actuation assembly of the TEMPO device is comprised ofvarious elements: the eductor, a diaphragm, a manifold, a trigger, and acradle. Inhalation through the mouthpiece causes air flow through theinhaler. A low pressure vacuum is created at the siphon hole of theeductor by the air flowing through the element. This vacuum “pulls” onthe diaphragm, which in turn causes the trigger to move. Trigger motionremoves the support from the cradle, which is then free to move underthe spring force. This motion causes the cradle to displace the filledcanister and results in drug formulation release through the valve. Theaction of closing the cocking lever releases the spring compression andcovers the mouthpiece.

The FCC of the TEMPO device is designed to slow and control thedischarged aerosol plume of formulation. This action allows forincreased residence time of the plume in the chamber, to promoteevaporation of propellant and to entrain the drug particles in theinhaled airflow. The FCC is comprised of several elements: a vortexplate; the FCC backwall/atomizing nozzle; a porous tube; and the FCCfront. An inhaled breath is directed through each of these elements.

The FCC vortex plate is located upstream of the atomizing nozzle. Aportion of the inhalation airflow is directed through the FCC vortexplate, causing the air to flow in a rotational (vortexing) pattern. Thisvortex action reduces the axial speed of the particles in the airstream,increasing residence time in the FCC to allow for propellantevaporation. The vortexing pattern is achieved by a proprietary vortexplate design.

The atomizing nozzle, integrated into the FCC backwall, releases anaerosol plume into the vortexing airflow created by the vortex plate.This mixture of aerosol and air from the vortex plate is slowed by theincrease in flow area within the FCC backwall/nozzle component. Inhaledair drawn through the vents of the FCC backwall/nozzle serves to (1)reduce overall flow resistance to improve patient comfort, and (2)provide sufficient axial momentum to drive the controlled, vortexingplume past the airflow entering through the FCC front and through themouthpiece, into the patient's respiratory tract.

Air is also drawn through the porous walls of the porous tube in theTEMPO device. This flow forms a cushioning layer along the inner wallsof the chamber, which inhibits deposition of aerosol on the walls.Another portion of the air pulled through the inhaler is drawn throughthe FCC front and is directed across the spray. This cross-flowimpinging jet slows the velocity of the aerosol plume, reducing theplume velocity to approximately the same velocity as the inhalation airflow.

A cutaway depiction of a BApMDI device incorporating an enhanced eductorproduced according to the present invention is depicted in FIG. 10. TheInhaler Device (500) includes an enhanced Eductor Element (510), and aPressurized Canister (520) that includes a Primeless Valve (530). TheInhaler Device (500) is readied for use by lifting and opening a CockingLever (550) through an angle of approximately 135 degrees. The action oflifting the lever uncovers the Mouthpiece (540) and readies the inhalerfor use. As the Cocking Lever (550) is lifted, cams on the levercompress two springs, which apply a force on a cradle holding thePressurized Canister (520) and provide the energy to actuate the filledcanister when the device is actuated. To operate the device, the patientcreates a seal with his or her lips around the edge of the Mouthpiece(540) and starts to take a normal inspiratory breath. As air flow isdrawn into the Inhaler Device (500) as depicted by the Arrows (A), theinspired air passes through the Enhanced Eductor (510) as depicted bythe Arrow (B), and provides a siphon pressure drop that is sufficient torelease the spring energy and cause the valve to discharge a dose of theaerosolized drug into a vortexing air flow depicted by the Arrow (E)which, after further vortexing in the FCC (560), exits the inhalerthrough the mouthpiece with the air flow depicted by Arrows (D),allowing inspiration of the drug into the patients' lungs.

EXAMPLES OF THE INVENTION Example 1. Production of an Enhanced EductorElement

An enhanced eductor in accordance with the present invention wasproduced from stock polycarbonate material using an injection moldingtechnique. The enhanced eductor element had the following relativephysical parameters:

the ratio between the height (H) of the protrusion (modification member)and the radius (R) of the constriction zone is between about 0.16 and0.65;

the ratio between the length of the protrusion (modification member)along the eductor long axis (L) and the length of the constriction zone(L_(CZ)) is between 0.25 and 0.75;

the spread of the protrusion (modification member) around the perimeterof the constriction zone radius (θ) is between 60 and 120 degrees; and

the reduction in the constriction zone cross-sectional area does notexceed about 21%.

In particular, on example of an enhanced eductor, “Rev003” asillustrated in FIGS. 5-6B had the following physical dimensions as setforth in Table 1 below:

TABLE 1 Eductor Feature Dimension Overall length of the eductor (L_(E))28.05 mm Inlet inside diameter (D_(i)) 6.62 mm Outlet inside diameter(D_(o)) 4.17 mm centerline of siphon from inlet 9.35 mm Start ofconstriction zone from inlet 5.74 mm diameter of siphon at inner surfaceopening 0.79 mm diameter of constriction zone (D_(t)) 2.53 mm length ofconstriction zone (L_(CZ)) 8.66 mm Modification member height (H) 0.40mm Displacement angle of the modification 66 degrees member (θ) Lengthof the modification member (L) 2.80 mm

Example 2. Pressure Drop Generated by the Enhanced Eductor Siphon

The siphon pressure drop, and the pressure drop across the eductor for aconventional eductor (Rev 002) and an enhanced eductor element (Rev 003)produced according to the present invention was estimated using standardmathematical techniques, and then those predicted values were comparedwith measured values. The Rev 002 and Rev 003 eductors had identicalprimary eductor parameters (identical eductor lengths (L_(E)), identicalinlet inside diameters (D_(i)), identical outlet inside diameters(D_(o)), identical throat diameters (D_(t)), and identical constrictionzone lengths (L_(CZ))). The predicted pressure drop values at variousfluid flow rates for the eductors were calculated using Bernoulli'sEquation:

ΔP _(siphon)=(P _(Ambient) −P _(Inlet Apex))=Q ²ρ(1/A ²−1/a ²)2g_(c)(g_(f)/cm²), where:

ρ=standard temperature and pressure (STP) air densitythroughout=0.001193 gm/cm³;

g_(c)=gravitational constant=982.14 (g_(m)/g_(f))(cm/sec²);

a=throat cross sectional area=πD_(t) ²/4; and

A=Inlet cross sectional area=% πD_(i) ²/4.

The predicted pressure drop values were then compared to the measuredperformance of the Rev 002 and Rev 003 eductors. The results of thecomparison are in Table 2, below.

TABLE 2 Unmodified Eductor Rev 002 Modified Eductor Rev 003 Bernoulli'sBemoulli's Equation Equation Measured Predicted Measured PredictedSiphon Siphon Eductor Siphon Siphon Eductor Flow Rate Pressure PressurePressure Pressure Pressure Pressure (Liters per Drop Drop Drop Drop DropDrop minute) (millibars) (millibars) ππ (millibars) (millibars)(millibars) π % (millibars) 10 8 8 -1% 5 10 10 6% 4 15 17 18 -3% 9 22 221% 7 20 31 32 -4% 16 40 39 1% 12 25 49 50 -2% 23 67 61 10% 18 30 71 72-1% 31 100 88 12% 26 35 99 98  1% 41 140 119 15% 38 40 133 128  4% 53191 156 19% 50 45 177 161  9% 70 260 197 24% 68 50 232 199 14% 96 351243 31% 93 53.2 280 226 19% 128 469 275 41% 126

The Δ% columns in Table 2 represent the percentage difference betweenthe Bernoulli's Equation-predicted Siphon Pressure Drop and the measuredSiphon Pressure Drop for the conventional eductor (Rev 002) and theenhanced eductor (Rev 003) that included a modification member per theinvention. As can be seen, Bernoulli's Equation accurately predicted thepressure drop over most of the range of flow rates (10 to 53.2 LPM) forthe conventional eductor (Rev 002), and thus the Δ% is small. However,for the enhanced eductor (Rev 003), Bernoulli's Equation did notaccurately predict the pressure drop, and the A % is thus large for themajority of the flow rates. The absolute increase in the Siphon PressureDrop for the enhanced eductor (Rev 003) is significantly larger thanwould have been expected or predicted based upon the current state ofthe art for eductor design.

Another unexpected benefit is that while the Siphon Pressure Drop wasincreased by effectively decreasing the constriction zone diameter inthe enhanced eductor (Rev 003), the Eductor Pressure Drop did notsubstantially increase at comparable flow rates. This runs counter towhat would be predicted by Poiseuelle's Equation, which would predictincreased Eductor Pressure Drop as the protrusion of the modificationmember into the constriction zone narrowed its' effective diameter. Theunexpected increase in Siphon Pressure Drop, with the unexpected lack ofincrease in the Eductor Pressure Drop is very beneficial for users of anBApMDI device employing an enhanced eductor in that it allows the userto trigger the device at lower flow rates with less effort. It has beenfound that the modification member protrusion can have a height as muchas 0.65 times the radius of the eductor constriction zone diameter, andreduce the cross-sectional area by up to about 21% without substantiallyaffecting the Eductor Pressure Drop (e.g., 10% or less), whileincreasing the Siphon Pressure Drop up to about 45% over a typical rangeof inhalation flow rates of 30-60 LPM.

While certain embodiments have been described herein, it will beunderstood by one skilled in the art that the methods, systems, andapparatus of the present disclosure may be embodied in other specificforms without departing from the spirit thereof. The present embodimentsare therefore to be considered in all respects as illustrative and notrestrictive of the present disclosure. Rather, the scope and spirit ofthe present invention is embodied by the appended claims.

What is claimed is:
 1. An enhanced eductor element comprising: a conduitcomprising an inner surface, an outer surface, an inlet, an outlet, anda hollow bore extending between the inlet and the outlet, the boretapering in a constriction zone between the inlet and the outlet; amodification member in the constriction zone and protruding from theinner surface to locally reduce a cross-sectional area of theconstriction zone; and a siphon channel providing fluid communicationbetween a siphon inlet at the conduit outer surface and a siphon outletat the conduit inner surface, the siphon outlet being positionedadjacent to the modification member; wherein the modification member isconfigured to increase a siphon pressure drop at the siphon inletwithout a substantial increase in a pressure drop across the eductorelement.
 2. The eductor element of claim 1, wherein the modificationmember comprises a bump on the inner surface of the conduit in theconstriction zone.
 3. The eductor element of claim 1, wherein themodification member comprises a conical bump and the siphon channelextends to an apex of the conical bump.
 4. The eductor element of claim1, wherein at least a portion of the modification member is disposedintermediate the conduit inlet and the siphon outlet in the constrictionzone.
 5. The eductor element of claim 1, wherein the siphon channelextends through the modification member to the inner surface.
 6. Theeductor element of claim 1, wherein the constriction zone defines afirst diameter, the first diameter being constant throughout theconstriction zone.
 7. The eductor element of claim 1, wherein theconstriction zone defines a first diameter that is smaller thandiameters of the bore at the inlet and at the outlet.
 8. The eductorelement of claim 1, wherein an inner surface of the bore defines agenerally smooth continuous curvilinear surface.
 9. The eductor elementof claim 1, wherein the modification member defines a height (H) and theconstriction zone defines a radius (R), wherein the modification memberheight (H) does not exceed 0.65 of the constriction zone radius (R). 10.The eductor element of claim 9, wherein a ratio of the modificationmember height (H) to the constriction zone radius (R) is between about0.16 and about 0.55.
 11. The eductor element of claim 1, wherein alength (L) of the modification member along a longitudinal axis of theeductor element and a length (Lcz) of the constriction zone along thelongitudinal axis, wherein the modification member length (L) does notexceed 0.75 of the constriction zone length (Lcz).
 12. The eductorelement of claim 11, wherein a ratio of the modification member length(L) to the constriction zone length (LCz) is between about 0.25 andabout 0.75.
 13. The eductor element of claim 1, wherein the modificationmember defines a length (L) along a longitudinal axis of the eductorelement and the constriction zone defines a radius (R), wherein a ratioof the modification member length (L) to the constriction zone radius(R) is between about 1.2 and about 3.0.
 14. The eductor element of claim1, wherein the modification member locally reduces the cross-sectionalarea of the constriction zone by 21% or less.
 15. The eductor element ofclaim 1, wherein a perimeter of the modification member extends alongbetween about 60 and about 120 degrees of a radius (R) of theconstriction zone.
 16. The eductor element of claim 1, wherein presenceof the modification member restricts airflow through the hollow bore by10% or less when compared to an eductor element without a modificationmember, but having the same inlet and outlet diameters, the sameconstriction zone diameter, and the same overall eductor length (LE) asthe eductor element.
 17. The eductor element of claim 1, wherein themodification member increases the siphon pressure drop as a function offlow rate.
 18. The eductor element of claim 1, wherein flow through thehollow bore is restricted by the modification member by no more than 10%when compared to an eductor element without the modification member. 19.A breath-actuated inhalation device comprising the eductor element ofclaim 1, wherein the conduit is not positioned along a medicament flowpath of the device.
 20. A breath-actuated inhalation device comprisingthe eductor element of claim 1, wherein air flowing through the eductorelement with an inspiratory breath, is sufficient to cause the siphonpressure drop and actuate the device.